Introduction: Intracanal medicaments play a vital role in disinfecting the root canals. Considering the ineffectiveness, potential side effects of synthetic drugs, the herbal alternatives for endodontic usage prove to be advantageous. Currently, very few pieces of literature are available on which combination of herbs are used as an intracanal medicament. Hence in this study, the effectiveness of neem, cinnamon and its combination against E.faecalis is evaluated. Aim: The objective of this study is to evaluate the antibacterial efficacy of neem, cinnamon and its combination and to compare these with chlorhexidine and calcium hydroxide as intracanal medicaments against Enterococcus faecalis (E. faecalis). Methodology: A total of 75 freshly extracted teeth specimens (n=15) were inoculated with E. faecalis for 21 days. Specimens were divided into five groups (Group 1: Neem paste, Group 2: Cinnamon paste, Group 3: Combination of Neem and Cinnamon paste, Group 4: Calcium hydroxide; Group 5: 2% chlorhexidine gel (CHX). The intra-canal medicaments were packed inside the tooth. After 7 days, the remaining microbial load was determined by using real-time PCR. Results: The threshold cycle (Ct) values of Neem, Cinnamon, Neem with Cinnamon, Calcium hydroxide __ampersandsignamp; 2% CHX were found to be 21.51, 20.48, 22.11, 22.46 __ampersandsignamp; 23.42 respectively. The mean bacterial load of these samples was 8.56, 12.45, 7.24, 0.83 __ampersandsignamp;0.13 respectively. Conclusion: Combination of Neem with Cinnamon has better antibacterial efficacy against E-Faecalis when compared to individual pastes of Neem and Cinnamon, the efficacy of the combination was comparable to that of calcium hydroxide. However, 2% Chlorhexidine had the highest antibacterial property.